Data collected in our laboratory and others have demonstrated a relationship between carbohydrate metabolism and perinatal growth and between dietary composition and endocrine status. This proposal is designed to study the metabolic-endocrine interaction in the regulation of fetal growth and development. The nutrients made available to the fetus are controlled largely by placental metabolism and maternal endocrine status. Fetal growth, maturation, survival, and body composition have been shown to be strongly influenced by diabetes and obesity during the third trimester of gestation. Maternal diabetes can be of several origins and may be precipitated by the metabolic and endocrine adjustments to gestation. It is further proposed that diet composition (i.e., high fat or high sucrose) may act to precipitate gestational diabetes. Our main objectives are as follows: 1) to characterize the ontogeny of placental enzyme and in vitro lipogenic and gluconeogenic activities in the pig; 2) to determine the mechanism(s) by which maternal hyper- and hypoglycemia alters (A) placenta, liver and adipose tissue metabolism, (B) maternal and fetal hormones; 3) to determine the influence of maternal diabetes and obesity on neonatal outcome and postnatal growth and glucose homeostasis at maturity; 4) to examine the short and long range influences (imprinting) of maternal diet composition on development of offspring; and 5) to determine the mechanism(s) by which diet composition influences gestational diabetes and diabetes mellitus in resulting offspring. Procedures for analysis of serum hormones (growth hormone, insulin, cortisol, T3, T4, and somatomedin) are operational in our laboratory. Methods in enzymology and tracer studies of metabolism have also been demonstrated. Experimental animals are readily available for these studies. Overall, the studies proposed here will provide for a clearer understanding of metabolic and endocrine regulation of fetal development in pregnancies which are complicated by diabetes of various etiologies.